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Conserved domains on  [gi|57242805|ref|NP_001008744|]
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tyrosyl-DNA phosphodiesterase 1 isoform a [Homo sapiens]

Protein Classification

tyrosyl-DNA phosphodiesterase 1( domain architecture ID 12068707)

tyrosyl-DNA phosphodiesterase 1 (TDP1) removes a variety of covalent adducts from DNA through hydrolysis of a 3'-phosphodiester bond, giving rise to DNA with a free 3' phosphate

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
Tyr-DNA_phospho pfam06087
Tyrosyl-DNA phosphodiesterase; Covalent intermediates between topoisomerase I and DNA can ...
166-582 0e+00

Tyrosyl-DNA phosphodiesterase; Covalent intermediates between topoisomerase I and DNA can become dead-end complexes that lead to cell death. Tyrosyl-DNA phosphodiesterase can hydrolyse the bond between topoisomerase I and DNA.


:

Pssm-ID: 461824 [Multi-domain]  Cd Length: 442  Bit Score: 549.18  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57242805   166 FYLTRVSGVKPKY--NSGALHIKDILSPLFgtLVSSAQFNYCFDVDWLVKQYPPEFRKKPILLVHGDKREA-KAHLHAQA 242
Cdd:pfam06087   2 FKLTRIRDLPETYnrNGDTITLKDILGDPL--LEESWLFNFQFDLDWLLSQFDPDVRLVKVTIVHGAWKEEnRLELLEKA 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57242805   243 KPYENISLCQAKLDIAFGTHHTKMMLLLYEE-GLRVVIHTSNLIHADWHQKTQGIWLSPLYPRIADGTHKSGESPTHFKA 321
Cdd:pfam06087  80 TIYPNVRLIFAYMPEPFGTHHSKMMILFYHDdSLRVVIPTANLIPYDWGNMTQGVWISPLLPLLPEASSSSGGSGTRFKR 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57242805   322 DLISYLMAYNAPSLKEWIDVIHKHDLSETNVYLIGSTPGRFQGSQKDNWGHFRLKKLLKDHASSMPNAES-WPVVGQFSS 400
Cdd:pfam06087 160 DLLRYLKAYGLPILKPLIDKLKKYDFSSVNVAFIASVPGRHKGSDADRWGWLKLAKALSSHPLLPPSDTSkWHIVAQTSS 239
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57242805   401 VGSLGADEsKWLCSEFKESMLTLG---------KESKTPGKSSVPLYLIYPSVENVRTSLEGYPAGGSLPYSIQTAEKQN 471
Cdd:pfam06087 240 IGSLGSTD-KWLKNEFTHSLSPALsgddgkeslSTTYKELKIKPRFKIIFPTVEEVRQSLDGYLSGGSIHFKYQSAQKQK 318
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57242805   472 WL---HSYFHKWSA--ETSGRSNAMPHIKTYMRP-SPDFSKIAWFLVTSANLSKAAWGALEKNGTQLMIRSYELGVLFLP 545
Cdd:pfam06087 319 QLyylKPYLCHWKQdpAKAGRKRAMPHIKTYIRFsSPDFKEIDWALLTSANLSKQAWGALEKNEGQLRIRNYELGVLFPP 398
                         410       420       430       440
                  ....*....|....*....|....*....|....*....|....
gi 57242805   546 SAFGLDSF---KVKQKFFAGSQEPMA----TFPVPYDLPPELYG 582
Cdd:pfam06087 399 KLFTGTDDfpeGSKLVPSTENDDEEDtfvvGVRVPYDLPLTPYG 442
 
Name Accession Description Interval E-value
Tyr-DNA_phospho pfam06087
Tyrosyl-DNA phosphodiesterase; Covalent intermediates between topoisomerase I and DNA can ...
166-582 0e+00

Tyrosyl-DNA phosphodiesterase; Covalent intermediates between topoisomerase I and DNA can become dead-end complexes that lead to cell death. Tyrosyl-DNA phosphodiesterase can hydrolyse the bond between topoisomerase I and DNA.


Pssm-ID: 461824 [Multi-domain]  Cd Length: 442  Bit Score: 549.18  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57242805   166 FYLTRVSGVKPKY--NSGALHIKDILSPLFgtLVSSAQFNYCFDVDWLVKQYPPEFRKKPILLVHGDKREA-KAHLHAQA 242
Cdd:pfam06087   2 FKLTRIRDLPETYnrNGDTITLKDILGDPL--LEESWLFNFQFDLDWLLSQFDPDVRLVKVTIVHGAWKEEnRLELLEKA 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57242805   243 KPYENISLCQAKLDIAFGTHHTKMMLLLYEE-GLRVVIHTSNLIHADWHQKTQGIWLSPLYPRIADGTHKSGESPTHFKA 321
Cdd:pfam06087  80 TIYPNVRLIFAYMPEPFGTHHSKMMILFYHDdSLRVVIPTANLIPYDWGNMTQGVWISPLLPLLPEASSSSGGSGTRFKR 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57242805   322 DLISYLMAYNAPSLKEWIDVIHKHDLSETNVYLIGSTPGRFQGSQKDNWGHFRLKKLLKDHASSMPNAES-WPVVGQFSS 400
Cdd:pfam06087 160 DLLRYLKAYGLPILKPLIDKLKKYDFSSVNVAFIASVPGRHKGSDADRWGWLKLAKALSSHPLLPPSDTSkWHIVAQTSS 239
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57242805   401 VGSLGADEsKWLCSEFKESMLTLG---------KESKTPGKSSVPLYLIYPSVENVRTSLEGYPAGGSLPYSIQTAEKQN 471
Cdd:pfam06087 240 IGSLGSTD-KWLKNEFTHSLSPALsgddgkeslSTTYKELKIKPRFKIIFPTVEEVRQSLDGYLSGGSIHFKYQSAQKQK 318
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57242805   472 WL---HSYFHKWSA--ETSGRSNAMPHIKTYMRP-SPDFSKIAWFLVTSANLSKAAWGALEKNGTQLMIRSYELGVLFLP 545
Cdd:pfam06087 319 QLyylKPYLCHWKQdpAKAGRKRAMPHIKTYIRFsSPDFKEIDWALLTSANLSKQAWGALEKNEGQLRIRNYELGVLFPP 398
                         410       420       430       440
                  ....*....|....*....|....*....|....*....|....
gi 57242805   546 SAFGLDSF---KVKQKFFAGSQEPMA----TFPVPYDLPPELYG 582
Cdd:pfam06087 399 KLFTGTDDfpeGSKLVPSTENDDEEDtfvvGVRVPYDLPLTPYG 442
PLDc_mTdp1_2 cd09195
Catalytic domain, repeat 2, of metazoan tyrosyl-DNA phosphodiesterase; Catalytic domain, ...
352-545 5.53e-124

Catalytic domain, repeat 2, of metazoan tyrosyl-DNA phosphodiesterase; Catalytic domain, repeat 2, of metazoan tyrosyl-DNA phosphodiesterase (Tdp1, EC 3.1.4.-). Human Tdp1 (hTdp1) acts as an important DNA repair enzyme with a preference for single-stranded or blunt-ended duplex oligonucleotides. It can remove stalled topoisomerase I-DNA complexes by catalyzing the hydrolysis of a phosphodiester bond between a tyrosine side chain and a DNA 3'-phosphate. It is therefore a potential molecular target for new anti-cancer drugs. hTdp1 has been shown to associate with additional proteins, such as XRCC1, to form a multi-enzyme complex. These additional proteins may be involved in recognizing 3'-phoshotyrosyl DNA in vivo. hTdp1 is a monomeric protein containing two copies of a variant HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue), which consists of the highly conserved histidine and lysine residues, but lacks the aspartate residue that is well conserved in other phospholipase D (PLD, EC 3.1.4.4) enzymes. Like other PLD enzymes, hTdp1 may utilize a common two-step general acid/base catalytic mechanism, involving a DNA-enzyme intermediate to cleave phosphodiester bonds. A single active site involved in phosphatidyl group transfer would be formed by the two variant HKD motifs from the N- and C-terminal domains in a pseudodimeric way.


Pssm-ID: 197291  Cd Length: 191  Bit Score: 363.54  E-value: 5.53e-124
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57242805 352 VYLIGSTPGRFQGSQKDNWGHFRLKKLLKDHASSMPNAESWPVVGQFSSVGSLGADESKWLCSEFKESmltLGKESKTPG 431
Cdd:cd09195   1 VFLIGSVPGRHTGSSLDKWGHLRLRKLLKEHASLPPVAESWPVIAQFSSIGSLGPDPQKWLCSEFLES---LSGLGKTSG 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57242805 432 KSSVPLYLIYPSVENVRTSLEGYPAGGSLPYSIQTAEKQNWLHSYFHKWSAETSGRSNAMPHIKTYMRPSPDFSKIAWFL 511
Cdd:cd09195  78 KSSPPLKLIYPSVENVRNSLEGYPAGGCLPYSKQTAEKQPWLKSYLHKWKADKRGRSRAMPHIKTYTRISPDLSKIAWFL 157
                       170       180       190
                ....*....|....*....|....*....|....
gi 57242805 512 VTSANLSKAAWGALEKNGTQLMIRSYELGVLFLP 545
Cdd:cd09195 158 LTSANLSKAAWGALEKNGTQLMIRSYEAGVLFLP 191
PRK08084 PRK08084
DnaA inactivator Hda;
429-491 4.95e-03

DnaA inactivator Hda;


Pssm-ID: 181224 [Multi-domain]  Cd Length: 235  Bit Score: 38.89  E-value: 4.95e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 57242805  429 TPGKSSVPLYLiyPSVEnvrTSLEGYPAG-GSLPYSIQTAEKQNwLHSYFHKWSAETSGRSNAM 491
Cdd:PRK08084   5 TPAQLSLPLYL--PDDE---TFASFYPGDnDSLLAALQNALRQE-HSGYIYLWSREGAGRSHLL 62
 
Name Accession Description Interval E-value
Tyr-DNA_phospho pfam06087
Tyrosyl-DNA phosphodiesterase; Covalent intermediates between topoisomerase I and DNA can ...
166-582 0e+00

Tyrosyl-DNA phosphodiesterase; Covalent intermediates between topoisomerase I and DNA can become dead-end complexes that lead to cell death. Tyrosyl-DNA phosphodiesterase can hydrolyse the bond between topoisomerase I and DNA.


Pssm-ID: 461824 [Multi-domain]  Cd Length: 442  Bit Score: 549.18  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57242805   166 FYLTRVSGVKPKY--NSGALHIKDILSPLFgtLVSSAQFNYCFDVDWLVKQYPPEFRKKPILLVHGDKREA-KAHLHAQA 242
Cdd:pfam06087   2 FKLTRIRDLPETYnrNGDTITLKDILGDPL--LEESWLFNFQFDLDWLLSQFDPDVRLVKVTIVHGAWKEEnRLELLEKA 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57242805   243 KPYENISLCQAKLDIAFGTHHTKMMLLLYEE-GLRVVIHTSNLIHADWHQKTQGIWLSPLYPRIADGTHKSGESPTHFKA 321
Cdd:pfam06087  80 TIYPNVRLIFAYMPEPFGTHHSKMMILFYHDdSLRVVIPTANLIPYDWGNMTQGVWISPLLPLLPEASSSSGGSGTRFKR 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57242805   322 DLISYLMAYNAPSLKEWIDVIHKHDLSETNVYLIGSTPGRFQGSQKDNWGHFRLKKLLKDHASSMPNAES-WPVVGQFSS 400
Cdd:pfam06087 160 DLLRYLKAYGLPILKPLIDKLKKYDFSSVNVAFIASVPGRHKGSDADRWGWLKLAKALSSHPLLPPSDTSkWHIVAQTSS 239
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57242805   401 VGSLGADEsKWLCSEFKESMLTLG---------KESKTPGKSSVPLYLIYPSVENVRTSLEGYPAGGSLPYSIQTAEKQN 471
Cdd:pfam06087 240 IGSLGSTD-KWLKNEFTHSLSPALsgddgkeslSTTYKELKIKPRFKIIFPTVEEVRQSLDGYLSGGSIHFKYQSAQKQK 318
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57242805   472 WL---HSYFHKWSA--ETSGRSNAMPHIKTYMRP-SPDFSKIAWFLVTSANLSKAAWGALEKNGTQLMIRSYELGVLFLP 545
Cdd:pfam06087 319 QLyylKPYLCHWKQdpAKAGRKRAMPHIKTYIRFsSPDFKEIDWALLTSANLSKQAWGALEKNEGQLRIRNYELGVLFPP 398
                         410       420       430       440
                  ....*....|....*....|....*....|....*....|....
gi 57242805   546 SAFGLDSF---KVKQKFFAGSQEPMA----TFPVPYDLPPELYG 582
Cdd:pfam06087 399 KLFTGTDDfpeGSKLVPSTENDDEEDtfvvGVRVPYDLPLTPYG 442
PLDc_mTdp1_2 cd09195
Catalytic domain, repeat 2, of metazoan tyrosyl-DNA phosphodiesterase; Catalytic domain, ...
352-545 5.53e-124

Catalytic domain, repeat 2, of metazoan tyrosyl-DNA phosphodiesterase; Catalytic domain, repeat 2, of metazoan tyrosyl-DNA phosphodiesterase (Tdp1, EC 3.1.4.-). Human Tdp1 (hTdp1) acts as an important DNA repair enzyme with a preference for single-stranded or blunt-ended duplex oligonucleotides. It can remove stalled topoisomerase I-DNA complexes by catalyzing the hydrolysis of a phosphodiester bond between a tyrosine side chain and a DNA 3'-phosphate. It is therefore a potential molecular target for new anti-cancer drugs. hTdp1 has been shown to associate with additional proteins, such as XRCC1, to form a multi-enzyme complex. These additional proteins may be involved in recognizing 3'-phoshotyrosyl DNA in vivo. hTdp1 is a monomeric protein containing two copies of a variant HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue), which consists of the highly conserved histidine and lysine residues, but lacks the aspartate residue that is well conserved in other phospholipase D (PLD, EC 3.1.4.4) enzymes. Like other PLD enzymes, hTdp1 may utilize a common two-step general acid/base catalytic mechanism, involving a DNA-enzyme intermediate to cleave phosphodiester bonds. A single active site involved in phosphatidyl group transfer would be formed by the two variant HKD motifs from the N- and C-terminal domains in a pseudodimeric way.


Pssm-ID: 197291  Cd Length: 191  Bit Score: 363.54  E-value: 5.53e-124
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57242805 352 VYLIGSTPGRFQGSQKDNWGHFRLKKLLKDHASSMPNAESWPVVGQFSSVGSLGADESKWLCSEFKESmltLGKESKTPG 431
Cdd:cd09195   1 VFLIGSVPGRHTGSSLDKWGHLRLRKLLKEHASLPPVAESWPVIAQFSSIGSLGPDPQKWLCSEFLES---LSGLGKTSG 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57242805 432 KSSVPLYLIYPSVENVRTSLEGYPAGGSLPYSIQTAEKQNWLHSYFHKWSAETSGRSNAMPHIKTYMRPSPDFSKIAWFL 511
Cdd:cd09195  78 KSSPPLKLIYPSVENVRNSLEGYPAGGCLPYSKQTAEKQPWLKSYLHKWKADKRGRSRAMPHIKTYTRISPDLSKIAWFL 157
                       170       180       190
                ....*....|....*....|....*....|....
gi 57242805 512 VTSANLSKAAWGALEKNGTQLMIRSYELGVLFLP 545
Cdd:cd09195 158 LTSANLSKAAWGALEKNGTQLMIRSYEAGVLFLP 191
PLDc_mTdp1_1 cd09193
Catalytic domain, repeat 1, of metazoan tyrosyl-DNA phosphodiesterase; Catalytic domain, ...
162-330 1.63e-94

Catalytic domain, repeat 1, of metazoan tyrosyl-DNA phosphodiesterase; Catalytic domain, repeat 1, of metazoan tyrosyl-DNA phosphodiesterase (Tdp1, EC 3.1.4.-). Human Tdp1 (hTdp1) acts as an important DNA repair enzyme with a preference for single-stranded or blunt-ended duplex oligonucleotides. It can remove stalled topoisomerase I-DNA complexes by catalyzing the hydrolysis of a phosphodiester bond between a tyrosine side chain and a DNA 3'-phosphate. It is therefore a potential molecular target for new anti-cancer drugs. hTdp1 has been shown to associate with additional proteins, such as XRCC1, to form a multi-enzyme complex. These additional proteins may be involved in recognizing 3'-phoshotyrosyl DNA in vivo. hTdp1 is a monomeric protein containing two copies of a variant HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue), which consists of the highly conserved histidine and lysine residues, but lacks the aspartate residue that is well conserved in other phospholipase D (PLD, EC 3.1.4.4) enzymes. Like other PLD enzymes, hTdp1 may utilize a common two-step general acid/base catalytic mechanism, involving a DNA-enzyme intermediate to cleave phosphodiester bonds. A single active site involved in phosphatidyl group transfer would be formed by the two variant HKD motifs from the N- and C-terminal domains in a pseudodimeric way.


Pssm-ID: 197289 [Multi-domain]  Cd Length: 169  Bit Score: 287.28  E-value: 1.63e-94
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57242805 162 NPFQFYLTRVSGVKPKYNSGALHIKDILSPLFGTLVSSAQFNYCFDVDWLVKQYPPEFRKKPILLVHGDKREAKAHlHAQ 241
Cdd:cd09193   1 PYFRFYTTKVGGIDTHYNPSSLSFKEILDPSLGELVSSLQFNFMFDIPWLVEQYPPELRNKPLTIVHGEKREPKAE-LAQ 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57242805 242 AKPYENISLCQAKLDIAFGTHHTKMMLLLYEEG-LRVVIHTSNLIHADWHQKTQGIWLSPLYPRIADGTHKSGESPTHFK 320
Cdd:cd09193  80 AKPYPNVTFCQAKLPIPFGTHHTKMMILLYEDGsLRVVISTANLIEDDWEQKTQGIWISPLLPRLSEDANSDGESPTGFK 159
                       170
                ....*....|
gi 57242805 321 ADLISYLMAY 330
Cdd:cd09193 160 ADLLEYLSSY 169
PLDc_Tdp1_2 cd09123
Catalytic domain, repeat 2, of tyrosyl-DNA phosphodiesterase; Catalytic domain, repeat 2, of ...
372-544 1.69e-65

Catalytic domain, repeat 2, of tyrosyl-DNA phosphodiesterase; Catalytic domain, repeat 2, of Tyrosyl-DNA phosphodiesterase (Tdp1, EC 3.1.4.-), which exists in eukaryotes but not in prokaryotes. Tdp1 acts as an important DNA repair enzyme that removes stalled topoisomerase I-DNA complexes by catalyzing the hydrolysis of a phosphodiester bond between a tyrosine side chain and a DNA 3'-phosphate. It is a monomeric protein that contains two copies of a variant HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue), which consists of the highly conserved histidine and lysine residues, but lacks the aspartate residue that is well conserved in other phospholipase D (PLD, EC 3.1.4.4) enzymes. Thus, this family represents a distinct class within the PLD superfamily. Like other PLD enzymes, Tdp1 may utilize a common two-step general acid/base catalytic mechanism, involving a DNA-enzyme intermediate to cleave phosphodiester bonds. A single active site involved in phosphatidyl group transfer would be formed by the two variant HKD motifs from the N- and C-terminal domains in a pseudodimeric way.


Pssm-ID: 197222  Cd Length: 182  Bit Score: 212.21  E-value: 1.69e-65
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57242805 372 HFRLKKLLKDHASSM-PNAESWPVVGQFSSVGSLGadeSKWLCSEFKESMLTLGKES-------KTPGKSSVPLYLIYPS 443
Cdd:cd09123   1 LGRLRKLLQNLTLDNkEKEKSKPLVYQFSSIGSLD---EKWWLNEFASSLGGVSSRSelplvkkNSPSLGKPKLKIIFPT 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57242805 444 VENVRTSLEGYPAGGSLPYSIQTAEKQNWLHSYFHKWSAETSG--RSNAMPHIKTYMRPSPD--FSKIAWFLVTSANLSK 519
Cdd:cd09123  78 VEEVRTSLEGYNGGGSIPFTIKNYESKEFLKKLFHRWKPRNNArrRQRAMPHIKTYIRYTDDgkIDKLGWVYLGSHNLSK 157
                       170       180
                ....*....|....*....|....*
gi 57242805 520 AAWGALEKNGTQLMIRSYELGVLFL 544
Cdd:cd09123 158 AAWGALQKNGSQLRIRNYELGVLFP 182
PLDc_Tdp1_1 cd09122
Catalytic domain, repeat 1, of Tyrosyl-DNA phosphodiesterase; Catalytic domain, repeat 1, of ...
183-327 1.27e-47

Catalytic domain, repeat 1, of Tyrosyl-DNA phosphodiesterase; Catalytic domain, repeat 1, of Tyrosyl-DNA phosphodiesterase (Tdp1, EC 3.1.4.-), which exists in eukaryotes but not in prokaryotes. Tdp1 acts as an important DNA repair enzyme that removes stalled topoisomerase I-DNA complexes by catalyzing the hydrolysis of a phosphodiester bond between a tyrosine side chain and a DNA 3'-phosphate. It is a monomeric protein that contains two copies of a variant HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue), which consists of the highly conserved histidine and lysine residues, but lacks the aspartate residue that is well conserved in other phospholipase D (PLD, EC 3.1.4.4) enzymes. Thus, this family represents a distinct class within the PLD superfamily. Like other PLD enzymes, Tdp1 may utilize a common two-step general acid/base catalytic mechanism, involving a DNA-enzyme intermediate to cleave phosphodiester bonds. A single active site involved in phosphatidyl group transfer would be formed by the two variant HKD motifs from the N- and C-terminal domains in a pseudodimeric way.


Pssm-ID: 197221  Cd Length: 145  Bit Score: 163.58  E-value: 1.27e-47
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57242805 183 LHIKDILSPLfgTLVSSAQFNYCFDVDWLVKQYPPEfRKKPILLVHGDKREAKAH--LHAQAKPYENISLCQAKLDIAFG 260
Cdd:cd09122   1 LSLKDLLGGD--DLESALLSSYMLDIDWLLSQLPLL-KIVPVTIVHGEKKEATKRasMIAQLNGLPNWTLVYPPLPGGYG 77
                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 57242805 261 THHTKMMLLLYEEGLRVVIHTSNLIHADWHQKTQGIWLSPLYPRIADGTH-KSGESPTHFKADLISYL 327
Cdd:cd09122  78 THHSKLILLKYPTGLRVVIPTANLTPYDWGEKSQGIWVQDFPLKNKRSASsGNNENPSDFKEDLIRFL 145
PLDc_yTdp1_1 cd09194
Catalytic domain, repeat 1, of yeast tyrosyl-DNA phosphodiesterase; Catalytic domain, repeat 1, ...
162-327 7.06e-35

Catalytic domain, repeat 1, of yeast tyrosyl-DNA phosphodiesterase; Catalytic domain, repeat 1, of yeast tyrosyl-DNA phosphodiesterase (yTdp1, EC 3.1.4.-). yTdp1 is involved in the repair of topoisomerase I DNA lesions by hydrolyzing the topoisomerase from the 3'-end of the DNA during double-strand break repair. Unlike human Tdp1 whose substrate-binding pocket can accommodate a fairly large topoisomerase I peptide fragment, yTdp1 has a preference for substrates containing one to four amino acid residues. The monomeric yTdp1 contains two copies of a variant HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue), which consists of the highly conserved histidine and lysine residues, but lacks the aspartate residue that is well conserved in other phospholipase D (PLD, EC 3.1.4.4) enzymes. Like other PLD enzymes, yTdp1 may utilize a common two-step general acid/base catalytic mechanism, involving a DNA-enzyme intermediate to cleave phosphodiester bonds. A single active site involved in phosphatidyl group transfer would be formed by the two variant HKD motifs from the N- and C-terminal domains in a pseudodimeric way.


Pssm-ID: 197290  Cd Length: 166  Bit Score: 129.33  E-value: 7.06e-35
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57242805 162 NPFQfyLTRVSGVKP--KYNSGALHIKDILSPlfGTLVSSAQFNYCFDVDWLVKQYPPEFRKKPILLVHGD--KREAKAH 237
Cdd:cd09194   1 SPFK--LVKSSAYDEeeEVNVDTITLKDLLGD--PDLKETWLFNFQYDLDFLLDQFHPNVNHVKITIVAGSgtIEPPTRR 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57242805 238 LHAQAKPYENISLCQAKLDIAFGTHHTKMMLLLYEEG-LRVVIHTSNLIHADWHQKTQGIWLSPLYPRIADGTHKSGESp 316
Cdd:cd09194  77 RIKLNKIYPNVKLIEAYMPPPFGTHHSKMMINFYQDDsCQIVIPSANLTEMDTNLPQQVVWKSPRLPLKSETVPGSGSR- 155
                       170
                ....*....|.
gi 57242805 317 thFKADLISYL 327
Cdd:cd09194 156 --FKRDLLAYL 164
PLDc_yTdp1_2 cd09196
Catalytic domain, repeat 2, of yeast tyrosyl-DNA phosphodiesterase; Catalytic domain, repeat 2, ...
438-545 9.49e-22

Catalytic domain, repeat 2, of yeast tyrosyl-DNA phosphodiesterase; Catalytic domain, repeat 2, of yeast tyrosyl-DNA phosphodiesterase (yTdp1, EC 3.1.4.-). yTdp1 is involved in the repair of topoisomerase I DNA lesions by hydrolyzing the topoisomerase from the 3'-end of the DNA during double-strand break repair. Unlike human Tdp1 whose substrate-binding pocket can accommodate a fairly large topoisomerase I peptide fragment, yTdp1 has a preference for substrates containing one to four amino acid residues. The monomeric yTdp1 contains two copies of a variant HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue), which consists of the highly conserved histidine and lysine residues, but lacks the aspartate residue that is well conserved in other phospholipase D (PLD, EC 3.1.4.4) enzymes. Like other PLD enzymes, yTdp1 may utilize a common two-step general acid/base catalytic mechanism, involving a DNA-enzyme intermediate to cleave phosphodiester bonds. A single active site involved in phosphatidyl group transfer would be formed by the two variant HKD motifs from the N- and C-terminal domains in a pseudodimeric way.


Pssm-ID: 197292  Cd Length: 200  Bit Score: 93.59  E-value: 9.49e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57242805 438 YLIYPSVENVRTSLEGYPAGGSLPYSIQTAEK------QNWLHSYFHKW--SAETSGRSNAMPHIKTYMRPSPD--FSKI 507
Cdd:cd09196  87 YIVYPTVEEIANSPVGWLSGGWFHFKYTRSDThknqyeQLRKNPYLYKWnsSDTTKGRERVPPHVKFYMCDNTDnwFKTL 166
                        90       100       110
                ....*....|....*....|....*....|....*...
gi 57242805 508 AWFLVTSANLSKAAWGAleKNGTQlmIRSYELGVLFLP 545
Cdd:cd09196 167 DWCLFTSANLSKQAWGT--PLSYK--PRNYELGVLYTS 200
PLDc_SF cd00138
Catalytic domain of phospholipase D superfamily proteins; Catalytic domain of phospholipase D ...
186-299 8.55e-05

Catalytic domain of phospholipase D superfamily proteins; Catalytic domain of phospholipase D (PLD) superfamily proteins. The PLD superfamily is composed of a large and diverse group of proteins including plant, mammalian and bacterial PLDs, bacterial cardiolipin (CL) synthases, bacterial phosphatidylserine synthases (PSS), eukaryotic phosphatidylglycerophosphate (PGP) synthase, eukaryotic tyrosyl-DNA phosphodiesterase 1 (Tdp1), and some bacterial endonucleases (Nuc and BfiI), among others. PLD enzymes hydrolyze phospholipid phosphodiester bonds to yield phosphatidic acid and a free polar head group. They can also catalyze the transphosphatidylation of phospholipids to acceptor alcohols. The majority of members in this superfamily contain a short conserved sequence motif (H-x-K-x(4)-D, where x represents any amino acid residue), called the HKD signature motif. There are varying expanded forms of this motif in different family members. Some members contain variant HKD motifs. Most PLD enzymes are monomeric proteins with two HKD motif-containing domains. Two HKD motifs from two domains form a single active site. Some PLD enzymes have only one copy of the HKD motif per subunit but form a functionally active dimer, which has a single active site at the dimer interface containing the two HKD motifs from both subunits. Different PLD enzymes may have evolved through domain fusion of a common catalytic core with separate substrate recognition domains. Despite their various catalytic functions and a very broad range of substrate specificities, the diverse group of PLD enzymes can bind to a phosphodiester moiety. Most of them are active as bi-lobed monomers or dimers, and may possess similar core structures for catalytic activity. They are generally thought to utilize a common two-step ping-pong catalytic mechanism, involving an enzyme-substrate intermediate, to cleave phosphodiester bonds. The two histidine residues from the two HKD motifs play key roles in the catalysis. Upon substrate binding, a histidine from one HKD motif could function as the nucleophile, attacking the phosphodiester bond to create a covalent phosphohistidine intermediate, while the other histidine residue from the second HKD motif could serve as a general acid, stabilizing the leaving group.


Pssm-ID: 197200 [Multi-domain]  Cd Length: 119  Bit Score: 42.50  E-value: 8.55e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57242805 186 KDILSPLFGTLVSSAQFNYCFD---VDWLVKQYPPEF-RKKPILLVHGDKREAKAHLHAQ---AKPYENISLCQAKLDIA 258
Cdd:cd00138   1 EALLELLKNAKESIFIATPNFSfnsADRLLKALLAAAeRGVDVRLIIDKPPNAAGSLSAAlleALLRAGVNVRSYVTPPH 80
                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 57242805 259 F-GTHHTKMMLLlyeEGLRVVIHTSNLIHADWHQKTQGIWLS 299
Cdd:cd00138  81 FfERLHAKVVVI---DGEVAYVGSANLSTASAAQNREAGVLV 119
PRK08084 PRK08084
DnaA inactivator Hda;
429-491 4.95e-03

DnaA inactivator Hda;


Pssm-ID: 181224 [Multi-domain]  Cd Length: 235  Bit Score: 38.89  E-value: 4.95e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 57242805  429 TPGKSSVPLYLiyPSVEnvrTSLEGYPAG-GSLPYSIQTAEKQNwLHSYFHKWSAETSGRSNAM 491
Cdd:PRK08084   5 TPAQLSLPLYL--PDDE---TFASFYPGDnDSLLAALQNALRQE-HSGYIYLWSREGAGRSHLL 62
PLDc_SF cd00138
Catalytic domain of phospholipase D superfamily proteins; Catalytic domain of phospholipase D ...
409-543 6.65e-03

Catalytic domain of phospholipase D superfamily proteins; Catalytic domain of phospholipase D (PLD) superfamily proteins. The PLD superfamily is composed of a large and diverse group of proteins including plant, mammalian and bacterial PLDs, bacterial cardiolipin (CL) synthases, bacterial phosphatidylserine synthases (PSS), eukaryotic phosphatidylglycerophosphate (PGP) synthase, eukaryotic tyrosyl-DNA phosphodiesterase 1 (Tdp1), and some bacterial endonucleases (Nuc and BfiI), among others. PLD enzymes hydrolyze phospholipid phosphodiester bonds to yield phosphatidic acid and a free polar head group. They can also catalyze the transphosphatidylation of phospholipids to acceptor alcohols. The majority of members in this superfamily contain a short conserved sequence motif (H-x-K-x(4)-D, where x represents any amino acid residue), called the HKD signature motif. There are varying expanded forms of this motif in different family members. Some members contain variant HKD motifs. Most PLD enzymes are monomeric proteins with two HKD motif-containing domains. Two HKD motifs from two domains form a single active site. Some PLD enzymes have only one copy of the HKD motif per subunit but form a functionally active dimer, which has a single active site at the dimer interface containing the two HKD motifs from both subunits. Different PLD enzymes may have evolved through domain fusion of a common catalytic core with separate substrate recognition domains. Despite their various catalytic functions and a very broad range of substrate specificities, the diverse group of PLD enzymes can bind to a phosphodiester moiety. Most of them are active as bi-lobed monomers or dimers, and may possess similar core structures for catalytic activity. They are generally thought to utilize a common two-step ping-pong catalytic mechanism, involving an enzyme-substrate intermediate, to cleave phosphodiester bonds. The two histidine residues from the two HKD motifs play key roles in the catalysis. Upon substrate binding, a histidine from one HKD motif could function as the nucleophile, attacking the phosphodiester bond to create a covalent phosphohistidine intermediate, while the other histidine residue from the second HKD motif could serve as a general acid, stabilizing the leaving group.


Pssm-ID: 197200 [Multi-domain]  Cd Length: 119  Bit Score: 37.11  E-value: 6.65e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57242805 409 SKWLCSEFKESMLTLGKesktpgkSSVPLYLIYPSVENVRTSLEGypaggslpysiQTAEKQNWLHSYFHKWsaETSGRS 488
Cdd:cd00138  22 SFNSADRLLKALLAAAE-------RGVDVRLIIDKPPNAAGSLSA-----------ALLEALLRAGVNVRSY--VTPPHF 81
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 57242805 489 NAMPHIKTYMRPSpdfskiAWFLVTSANLSKAAWGalekngtqlmiRSYELGVLF 543
Cdd:cd00138  82 FERLHAKVVVIDG------EVAYVGSANLSTASAA-----------QNREAGVLV 119
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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